Impact of Obesity on Chemotherapy Pharmacokinetics, Toxicity, and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia.
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Obesity is increasingly prevalent among children and adolescents and may influence chemotherapy pharmacokinetics, treatment-related toxicity, and clinical outcomes in pediatric acute lymphoblastic leukemia (ALL). This narrative review evaluates current evidence regarding the effects of obesity on drug disposition, chemotherapy-associated toxicity, dosing considerations, and survival outcomes in pediatric ALL. Obesity alters body composition and may affect hepatic and renal physiology; however, its pharmacokinetic effects vary among therapeutic agents. Studies demonstrate associations between greater body size or adiposity and delayed high-dose methotrexate elimination, modestly reduced pegaspargase clearance, and lower thioguanine nucleotide concentrations during mercaptopurine maintenance, although these findings have not consistently translated into differences in systemic exposure or treatment efficacy. Obesity has also been associated with hepatotoxicity, pancreatitis, conjugated hyperbilirubinemia, and vincristine-induced peripheral neuropathy. Importantly, persistent overweight or obesity and extreme obesity have been associated with inferior survival outcomes or increased relapse risk in some cohorts, although the mechanisms underlying these associations remain incompletely understood. Current evidence does not support generalized chemotherapy dose reduction based solely on obesity. Instead, management should remain drug- and protocol-specific and incorporate organ function, pharmacogenetics, therapeutic drug monitoring when available, and observed toxicity. Prospective studies integrating longitudinal body composition with pharmacokinetic, pharmacodynamic, toxicity, and survival measures are needed to define whether specific patient subgroups may benefit from individualized dosing strategies.